Chen J, Zhou S-N, Zhang Y-M, Feng Y-L, Wang S
Department of Neurology, Qilu Hospital of Shandong University, Jinan, China. & Brain Science Research Institute, Shandong University, Shandong, P.R. China.
Eur Rev Med Pharmacol Sci. 2015 Apr;19(7):1234-40.
Glycosides of cistanche (GC) is extracted from Xin Jiang Cistanche, which is widely used as a Chinese herb. This study aims to evaluate the effects of GC on vascular dementia (VD).
The VD model was established by the ligature of the bilateral common carotid artery in adult Wistar rats, who received daily i. p. administration of saline, GC (10 mg/kg body weight/d, i.p.) or oxiracetam (450 mg/kg body weight/d, i.p) for 14 days. Morris Water Maze test valued cognitive performance of the rats. The hippocampus was dissected and subjected to proteomics and immunohistochemical analysis.
The GC group showed significantly lower escape latency than the VD group at four and five days after surgery. They showed no significant difference when compared with sham-operated group and the oxiracetam control group. In the hippocampus, the 21 protein spots in the GC group showed different expression levels compared with the VD group. This included the four proteins that showed a significant difference: three upregulated proteins thioredoxin-like protein 1, dual specificity mitogen-activated protein kinase kinase 1 and dihydropyrimidinase-related protein 2 (CRMP-2), and one down-regulated protein glutathione synthetase. Immunohistochemistry analysis showed that P-tau protein level was significantly higher in the VD model group than the sham-operated group (p < 0.05). After GC treatment, P-tau protein level in VD model rats showed a significant decrease compared with VD group treated with saline (p < 0.05).
The GC plays a critical role in protecting the hippocampal neurons in the VD, by decreasing P-tau phosphorylation and increasing the CRMP-2 expression level. Pharmacological manipulation of GC offers a new opportunity for VD treatment.
肉苁蓉苷（GC）从新疆肉苁蓉中提取，肉苁蓉作为一种中草药被广泛使用。本研究旨在评估GC对血管性痴呆（VD）的影响。
通过结扎成年Wistar大鼠双侧颈总动脉建立VD模型，将大鼠分为三组，分别每日腹腔注射生理盐水、GC（10mg/kg体重/天，腹腔注射）或奥拉西坦（450mg/kg体重/天，腹腔注射），持续14天。采用Morris水迷宫试验评估大鼠的认知能力。解剖大鼠海马进行蛋白质组学和免疫组织化学分析。
术后第4天和第5天，GC组大鼠的逃避潜伏期显著低于VD组。与假手术组和奥拉西坦对照组相比，无显著差异。在海马中，GC组与VD组相比有21个蛋白点表达水平不同。其中有4种蛋白差异显著：3种上调蛋白，即硫氧还蛋白样蛋白1、双特异性丝裂原活化蛋白激酶激酶1和二氢嘧啶酶相关蛋白2（CRMP-2），以及1种下调蛋白谷胱甘肽合成酶。免疫组织化学分析显示，VD模型组的P- tau蛋白水平显著高于假手术组（p<0.05）。GC治疗后，VD模型大鼠的P- tau蛋白水平与生理盐水处理的VD组相比显著降低（p<0.05）。
GC通过降低P- tau磷酸化水平和提高CRMP-2表达水平，对VD大鼠海马神经元具有关键的保护作用。GC的药理调控为VD治疗提供了新的机会。
